Collectively, these data reveal strong differences in the role of the p53/p21 axis for the anti-proliferative and pro-senescent effects of E6AP or E6/E7 repression in HPV-positive cancer cells, since these phenotypic responses are highly dependent on p53 and p21 induction upon E6AP repression, but not upon E6/E7 repression. The gene discussed is TP53; the disease is cancer.